We provided mice with free access to two different obesigenic diets followed by a switch to chow to see if obesity was reversed. Specifically, 71 male C57BL/6 mice were individually-housed and after 6 mice were euthanized for baseline measurements the remaining mice were randomly assigned to five groups: 1) C group (N=18) continued on the chow diet;2) HF group (N=18) on a 60% high fat diet;3) HFL group (N=17) on the high fat diet plus liquid Ensure;4) HF-C group (N=6) switched from high fat to chow after 7 weeks;5) HFL-C group (N=6) switched from high fat plus Ensure to chow after 7 weeks. Body weight was increased after 7 weeks on both obesigenic diets, with the Ensure supplemented group gaining the most weight and corresponded to elevated concentrations of serum insulin, glucose, and leptin and paradoxically lower serum triglycerides. Development of obesity was caused by increased energy intake and a relative decrease of average energy output along with decreased locomotor activity. Twelve weeks after the switch to chow, the HF-C and HFL-C groups lost weight but maintained the same level of persistent obesity vs. control (34.81.2, 34.11.2 vs. 30.80.8 g respectively;P <0.05). All serum hormones and metabolites returned to control levels with the exception for a slight increase of leptin. After the diet switch, the HF-C and HFL-C groups had an average energy output in line with the C group and the persistent obesity was maintained despite less than 1 kcal/d of additional energy intake.